Bile Acid-Based 1,2,4-Trioxanes: Synthesis and Antimalarial Assessment

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• 作者：Chandan Singh ; Mohammad Hassam ; Ved Prakash Verma ; Ajit Shanker Singh ; Niraj Krishna Naikade ; Sunil K. Puri ; Prakas R. Maulik ; Ruchir Kant
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：December 13, 2012
• 年：2012
• 卷：55
• 期：23
• 页码：10662-10673
• 全文大小：492K
• 年卷期：v.55,no.23(December 13, 2012)
• ISSN：1520-4804

文摘

A new series of bile acid-based trioxanes 23a鈥?b>d, 24a鈥?b>d, 25a鈥?b>d, 26a, 26b, and 26d have been synthesized and assessed for their antimalarial activity against multidrug-resistant Plasmodium yoelii in Swiss mice by oral route. The antimalarial activity of these trioxanes showed a strong dependence on the side-chain length; shortening side-chain length lead to increase in activity. The antimalarial activity also showed even stronger dependence on the stereochemistry at C3 and C6 (C21 in Figure 5) of the trioxane moiety. Of the two diastereomers isolated of each of the trioxanes, more polar one was significantly more active than the less polar one. The more polar diastereomer of the trioxanes 26a, 26b, and 26d, were the most active compounds of the series. All these three trioxanes provided 100% protection at 24 mg/kg 脳 4 days. In this model 尾-arteether provided 100% and 20% protection at 48 mg/kg 脳 4 days and 24 mg/kg 脳 4 days, respectively.